In the mammalian CANS, the probability that an action potential will trigger neurotransmitter release (P1) varies widely form synapse to synapse. The aim of this research is to ascertain the mechanisms underlying the differences in release probability between synaptic terminals. The basis of functional presynaptic heterogeneity will be studied by comparing lateral (facilitating; low P) and medial (non- facilitating ; high P) perforant path synapses using whole-cell recording of synaptic responses in hippocampal slices, optical recording of presynaptic calcium transients, and electron microscopy. The main hypothesis to be tested are that differences in calcium influx and the number of docked vesicles underlie the different release properties of lateral perforant path terminals . the specific aims are: 1. To quantify the probability or release at lateral and medial perforant path synapses, and determine if a difference n release probability along can account for the difference in paired-pulse plasticity. 2. To determine if the difference in the probability of relate sat lateral and medial perforant path synapses results from a difference in presynaptic calcium influx. 3. To determine if the difference in the probability of release at lateral and medial perforant path synapses results from a difference in a number of docked vesicles. These experiments will provide information about the mechanisms that dictate function at excitatory presynaptic terminals in the adults CANS. These mechanisms are likely to be critically important for normal information processing, and may be altered during plastic changes that accompany information storage and pathological processes.